Different systems have been developed for the delivery of pharmaceutical agents. One such system operates by means of a complicated osmotic pumping mechanism which is expensive and often difficult to prepare. Also known are delivery devices made of matrices using hydrogels. These devices use one or more hydrogels either selected from uncrosslinked linear polymers or from crosslinked polymers. None use both types of polymers in a single device.
While these systems do act to deliver selected pharmaceuticals, they do not provide for controlled release of the pharmaceutical in a sustained or pulsatile mariner for a predetermined period of time. In devices using uncrosslinked polymers, viscosity is the rate controlling factor for drug release kinetics. In these systems a gelatinous layer is formed on the surface upon hydration. The thickness and durability of this gelatinous layer depends upon the concentration, as well as the molecular weight and viscosity of the polymer in the device. At higher concentrations the linear polymer chains entangle to a greater degree leading to virtual crosslinking and a stronger gel layer. Drug release is effected by the dissolution of the polymer and erosion of the gel layer. Hence the rate of erosion controls the release rate.
In the case of devices using covalently crosslinked polymers, the drug is trapped in a glassy core in the dry state. On contact with an aqueous medium the surface of the device is hydrated to form a gelatinous layer which is different from the gel layer seen in uncrosslinked linear polymers. The hydrogel formed by crosslinked polymers does not consist of entangled chains but discrete microgels made up of many polymer particles, called a crosslinked network, in which the drug is dispersed. Therefore drug is trapped in the hydrogel domains. These hydrogels are not water soluble and do not dissolve, thus erosion as seen in uncrosslinked linear polymers does not occur. Drug release is by the osmotic pressure generated within the fully hydrated hydrogel which works to break up the structure by sloughing off discrete pieces of the hydrogel. The hydrogels remain intact while drug continues to diffuse through the gel layer at uniform rate.
U.S. Pat. Nos. 3,845,770, 3,916,899, 4,016,880, 4,160,452 and 4,200,098 disclose such delivery systems as described above. However, none of these patents teach the use of both covalently, crosslinked and uncrosslinked linear polymers in combination in a single delivery device for the controlled or pulsatile delivery of pharmaceutically active agents thereby taking advantage of their unique but different properties and mechanism of drug release.